Molecular basis of mechanosensory transduction

Gillespie, Peter G.; Walker, Richard G.

doi:10.1038/35093011

Cited by 645 publications

(493 citation statements)

References 96 publications

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“…In order to enable a broad range of functions, such as cell motility, transport across ion-channels, or the formation of active enzymatic pockets, living organisms rely on mechanochemical transduction schemes that are based on a multitude of non-covalent interactions. 1,10 Non-covalent interactions have also emerged as a useful design tool for stimuli-responsive functional polymers. 11 Notable examples include mechanochromic blends containing selfassembled excimer-forming dyes that can be dispersed upon mechanical deformation, 12 healable polymers based on supramolecular motifs, which are presumed to dissociate upon application of excessive mechanical force, 13 and the mechanochemically activated dissociation of coordination polymers, which are useful for mechanically activated catalysis.…”

Section: Introductionmentioning

confidence: 99%

Mechanochemistry with Metallosupramolecular Polymers

et al. 2014

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ABSTRACT:The transduction of mechanical force into useful chemical reactions is an emerging design approach to impart soft materials with new functions. Here, we report that mechanochemical transductions can be achieved in metallosupramolecular polymers. We show that both reversible and irreversible reactions are possible and useful to create mechanically responsive materials that display new functions. The metallopolymer studied was a crosslinked network assembled from a europium salt and a telechelic poly(ethylene-co-butylene) with 2,6-bis(1′-methylbenzimidazolyl)pyridine (Mebip) ligands at the termini. The Eu 3+ complexes serve both as mechanically responsive binding motifs and built-in optical probes that can monitor the extent of (dis)assembly due to their characteristic photoluminescent properties. Indeed, dose-dependent and reversible metal-ligand dissociation occurs upon exposure to ultrasound in solution. The absence of ultrasound-induced dissociation of a low-molecular weight model complex and in-depth studies of temperature effects confirm that the dissociation is indeed the result of mechanical activation. The influence of the strength of the metal-ligand interactions on the mechanically induced dissociation was also explored. Metallopolymers in which the Mebip ligands were substituted with more strongly coordinating dipicolinate (dpa) ligands do not dissociate upon exposure to ultrasound. Finally we show that mechanochemical transduction in metallosupramolecular polymers is also possible in the solid state. We demonstrate mending of damaged objects through ultrasound as well as mechanochromic behavior based on metal-exchange reactions in metallopolymers imbibed with an auxiliary metal salt.

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Section: Introductionmentioning

confidence: 99%

Mechanochemistry with Metallosupramolecular Polymers

et al. 2014

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“…Mechanotransduction concerns the cellular responses to a variety of mechanical stimuli [1][2][3][4][5][6][7]. Specialized mechano-sensitive cells, such as hair cells in the inner ear or dorsal root ganglion touch receptors, are equipped with highly sensitive transduction channel complexes.…”

Section: Introductionmentioning

confidence: 99%

Piezo1‐dependent stretch‐activated channels are inhibited by Polycystin‐2 in renal tubular epithelial cells

et al. 2013

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Mechanical forces associated with fluid flow and/or circumferential stretch are sensed by renal epithelial cells and contribute to both adaptive or disease states. Non-selective stretch-activated ion channels (SACs), characterized by a lack of inactivation and a remarkably slow deactivation, are active at the basolateral side of renal proximal convoluted tubules. Knockdown of Piezo1 strongly reduces SAC activity in proximal convoluted tubule epithelial cells. Similarly, overexpression of Polycystin-2 (PC2) or, to a greater extent its pathogenic mutant PC2-740X, impairs native SACs. Moreover, PC2 inhibits exogenous Piezo1 SAC activity. PC2 coimmunoprecipitates with Piezo1 and deletion of its N-terminal domain prevents both this interaction and inhibition of SAC activity. These findings indicate that renal SACs depend on Piezo1, but are critically conditioned by PC2.

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“…With this in mind, we investigated in this study whether an agerelated decline in afferent sensitivity correlates with altered expression of membrane channel proteins. We focused on the thermosensitive ion channels in the transient receptor potential (TRP) family and the tetrototoxin resistant sodium channels since these channels are involved in the generation and transmission of impulse trains in response to mechanical and thermal stimuli [19,23]. Effects of aging on electrical membrane properties (EMP) of mouse DRG neurons in culture have indicated that neurons of aged animals (22-23-month old) exhibit decreased electrical excitability and increased action potential duration compared to younger animals (2-3.5-month old) [33].…”

Section: Introductionmentioning

confidence: 99%

Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice

Wang

Davis

Zwick³

et al. 2006

Neurobiology of Aging

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Sensory neurons in aging mammals undergo changes in anatomy, physiology and gene expression that correlate with reduced sensory perception. In this study we compared young and aged mice to identify proteins that might contribute to this loss of sensation. We first show using behavioral testing that thermal sensitivity in aged male and female mice is reduced. Expression of sodium channel (Nav1.8 and Nav1.9) and transient receptor potential vanilloid (TRPV) channels in DRG and peripheral nerves of young and old male mice was then examined. Immunoblotting and RT-PCR assays showed reduced Nav1.8 levels in aged mice. No change was measured in TRPV1 mRNA levels in DRG though TRPV1 protein appeared reduced in the DRG and peripheral nerves. The GFRα3 receptor, which binds the growth factor artemin and is expressed by TRPV1-positive neurons, was also decreased in the DRG of aged animals. These findings indicate that loss of thermal sensitivity in aging animals may result from a decreased level of TRPV1 and Nav1.8 and decreased trophic support that inhibits efficient transport of channel proteins to peripheral afferents.

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Molecular basis of mechanosensory transduction

Cited by 645 publications

References 96 publications

Mechanochemistry with Metallosupramolecular Polymers

Mechanochemistry with Metallosupramolecular Polymers

Piezo1‐dependent stretch‐activated channels are inhibited by Polycystin‐2 in renal tubular epithelial cells

Reduced thermal sensitivity and Nav1.8 and TRPV1 channel expression in sensory neurons of aged mice

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